Suicide inhibition of alpha-oxamine synthases: structures of the covalent adducts of 8-amino-7-oxononanoate synthase with trifluoroalanine

Org Biomol Chem. 2006 Apr 7;4(7):1209-12. doi: 10.1039/b517922j. Epub 2006 Mar 1.

Abstract

The irreversible inhibition of 8-amino-7-oxononanoate synthase by trifluoroalanine involves decarboxylative defluorination of the inhibitor-PLP aldimine followed by attack of the conjugated imine by the amino group of the active site lysine to afford a covalently bound difluorinated intermediate which can subsequently undergo further HF losses and hydrolysis to afford a 2-(pyridoximine phosphate) acetoyl protein adduct.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases / antagonists & inhibitors
  • Acyltransferases / chemistry*
  • Acyltransferases / metabolism*
  • Alanine / analogs & derivatives*
  • Alanine / metabolism*
  • Binding Sites
  • Catalysis
  • Hydrolysis
  • Ligases / antagonists & inhibitors*
  • Lysine / chemistry
  • Models, Molecular
  • Protein Conformation

Substances

  • Acyltransferases
  • 8-amino-7-oxononanoate synthase
  • Ligases
  • Lysine
  • Alanine